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TH E RELATIONSHI P O F EVENT-RELATE D BRAI NPOTENTIAL S AN D LEA D ABSORPTION : AREVIE WO F CURRENT 1 EVIDENCE * 

## (S^^CL^ J

Davi d A . Otto , Ph.D .

Neurotoxicolog

yDivisio n Healt hEffect s Researc hLaboratory Researc hTriangl e Park , NC 2771 1

T o appea r in : L . Vysock i fi: L . Goldwate r (eds. ) Lea d Environmenta l Health : Th e Curren t Issue s

^Thi s articl e ha s bee n reviewe d b yth e Healt hEffect s Researc hLaboratory , U.S . Environmenta l Protectio n Agenc yan d approve d fo r publication . Approva l doe s no t signif ytha t th e content s necessaril yreflec t th e view s an d policie s o f th e Agency . 

## 01P. 3

,1 ! Sensor yevoked an

d slowbrai n potentials , collectivel ykriow n a s event-relate d potential s (ERPs) , hav e bee n use d during th e pas t decad e t o stud yth e effect s o f lead exposur e on centra l nervou s systemfunctio n i n hunan s an

d animals . Th e objective s o f thi s pape r ar e t o reviewthes e studies , t o conside r th e healt himplication s o f thes e data , an d t o sugges t futur e direction s fo r neurobehaviora l studie s o f lea d effect s i n humans . ANIMA L STUDIE S 

# w

Th e effect s o f lead exposur e on flas hevoke d potential s (FEP ) i n rat s hav e bee n studie d b yFo xe t a l (1977 , 1979) , Feeneye t a l (19?9 ) an d Winnek e (1979) . Importan t methodologica l detail s an d result s o f thes e studie s ar e summarize d i n Tabl e I . Althoughlead-relate d change s i n FE P latencyo r amplitud e wer e observe d i n eac ho f thes e studies , th e patter n o f effect s wa s inconsisten t acros s studies . Fo r instance , Fo xe t a l (1977 ) reporte d increase d latencie s (conponent s Pl , Nl , P2 , N2) , Feeneye t a l reporte d decrease d (P2 ) latency , an d Winnek e foun

d n o latencychang e i n Pb-expose d animal s compare d t o controls . Winneke , on th e othe r hand , observe d depresse d FE P amplitudes , whil e Fo xe t a l (1979 ) observe d increase d amplitud e recovery (cortica l excitability ) t o paire d flashe s i n Pb-expose d rat s relativ e t o controls . Afurthe r puzzling inconsistencyexist s i n th e report s o f Fo xe t a l (19 7 7 vs . 1979) . Th e effec t o f P bexposur e on th e recover yfunctio n o f visua l corte xwa s evaluate d i n bot hstudie s —apparentl yi n th e same animals . Fo xe t a l (1977 ) reporte d decrease d CN S recoverybase d on latencymeasures , whil e Fo xe t a l (1979 ) reporte d increase d CN S recover y (excitability ) base d on amplitud e measure s i n Pb-expose d animal s compare d t o controls . Th e author s mak e n o effor t t o reconcil e thes e clearl y discrepan t findings .P. 4

•



### Inconsisten t FE P finding s co\ild b e du e t o a variet yo f methodologica l

difference s amon g studies . Th e Hoses , duratio no f materna l and offsprin g exposure , ag e a t testing , specie s o r strain s o f rats , and electrophysiologica l testin g method s varie d considerabl yamon g investigators . Result s o f thes e studie s d o suggest , however , tha t neonata l P bexposur e produce d persisten t effect s o nvisua l syste mfunctio ni nadul t rats . HUMANSTUDIE S Durin g th e pas t eigh t year s a serie s o f collaborativ e studie s byth e Universit yo f Nort hCarolin a and th e U.S . Environmenta l Protectio n Agenc y hav e bee nundertake nt o explor e th e effect s o f asymptomatic.lea d exposur e o nneurobehaviora l functio ni nchildren . Thre e evaluation s wer e mad e o f on e group o f childre nincludin g a n initia l assessmen t i n 1978-7 9 (Ott o e t a l 19R1) , a two-yea r follow-u p i n198 0 (Ott o e t a l 1082) , and a five-yea r follow-u p i n198 3 (Ott o e t a l I985 , Schroede r e t al , I985) . Areplicatio n studyi na nindependen t group o f childre nwa s complete d i n1981 * (Haw k e t a l 19^5 ; Robinso ne t a l 1985) . Th e electrophysiologica l result s o f thes e studie s wil l b e reviewe d below . '' . -. Tw o primar ysource s o f exposur e wer e identifie d i nth e origina l studygroup : (l ) lead-contaminate d dus t transmitte d int o home s o nth e clothin g o f worker s fro ma batter ymanufacturin g plant ; and (2 ) lead

base d pain t prevalen t i nhome s buil t prio r t o 1950 . I t shoul d b e note d tha t th e soi l aroun d home s wit hlead-base d exterio r pain t ma yb e con taminate d fro m

weatherin g eve n i nth e absenc e o f peelin g paint . Th e primar y sourc e o f exposur e i nth e replicatio n studywa s lead-base d paint . Th e primar yrout e o f exposur e i nal l case s wa s ingestion .P. 5

'if I I

highe r tha ni nthe replicatio ngroupdu e t o employmen t i nthe batter y plant . Almos t al l parent s o f childre ni nthe secon dgroupwer e unemploye d (Hollingshea dClas s V) . Childre nrange di nag e fro m 1 t o 6 year s i nth e initia l evaluation , 3 t o 7 year s a t two-yea r follow-up , 6 t o 1 2 year s a t five-yea r follow-up , an d3 t o 7 i nth e replicatio nstudy. Se e Mila r e t a l (1980 ) an

dHaw ke t a l (1985 ) fo r additiona l demographi c details . Tabl e I I summarize s the exposure , medical , psychometric , an ddemo graphi c measure s obtaine dfro m childre nan

dparent s i nthi s serie s o f studies . Childre nwit han y acut e illness , histor y o f perinata l trauma , iro ndeficienc y

neurologica l disorder , o r frankmenta l retardatio n(1 0 < 60 )

wer e exclude dfro m dat a analyses . Socio-economi c status , H.O.M.E . scores , materna l 10 , ag e an dgende r wer e use da s covariate s o r contro l variable s i nstatistica l analyse s o f electrophysiologica l data . Severa l differen t electrophysiologica l test s wer e use di nthes e studies : sensor y

conditionin g (active an dpassive) , pattern-reversa l visua l evoke d potentia l (PREP) , an dbrainstem

auditory

evoke dpotentia l (BAEP) . Methodo logica l detail s o f thes e test s ar e provide di nOtt o e t a l (1985) . .Th e onl y tes t use di nal l evaluation s wa s passiv e sensory conditioning . Activ e sensor y

conditionin g wa s use donl y i nthe five-yea r follow-upstud y becaus e childre nunde r five year s o f ag e do no t butto npres s reliably . The PRE P

an dBAE P wer e use di nthe five-yea r follow-upan dreplicatio nstudies . Result s o f thes e test s wil l b e reviewe dan ddiscusse dbelow . Slo w wav e voltag e durin g sensor y conditioning . Electrica l activit y o f the brai nwa s recorde dfro m the verte xo f childre nwhil e they watche d silen t cartoons . A warnin g ton e wa s presente da t rando m interval s signallin g tha t the cartoo nwoul db e interrupte dbriefly . Thi s tes tP. 6

i s a formo f classica l conditioning i n whic hth e warnin g ton e i s a conditiona l stimulu s (OS ) whic hi s paire d wit ha mildl yaversiv e uncon ditiona l stimulu s (UCS) , th e cartoo n interruption . Electrica l activit y (slo wwav e voltage ) wa s recorde d during th e CS-UC S interva l an d average d acros s successive trial s (1-3 5 i n th e initia l evaluation ; 1-5 0 an d 50-10 0 i n late r evaluations) . Slo wwav e voltag e during th e CS-UC S interva l i s assume d t o b e an electrophysiologica l correlat e o f conditioning —i.e. , th e chil d learn s t o anticipat e tha t th e cartoo n wil l b e interrupte d whe n th e warning signa l i s presented . I n th e passiv e test , however , ther e i s n o behaviora l measur e o f conditioning t o validat e thi s inference . Th e functiona l significanc e o f thi s measur e o f slowwav e voltage , therefore , remain s uncertai n i n th e passiv e test . Result s o f sensor

yconditioning test s i n thi s serie s o f studie s ar e summarize d i n Tabl e III . Th e initia l evaluatio n (Ott o e t al , 198l ) indicate d tha t slowwav e voltag e varie d a s a linea r functio n o f bloo d lead (PbB ) leve l an

d tha t th e slop e o f thi s functio n varie d wit hag e a s show n in Figur e 1 . Result s o f th e two-yea r follow-u p stud yshowe d a simila r ag e x PbB interactio n o f slowwav e voltag e during passiv e sensor yconditioning (Ott o e t al , 1982) . Slowwav e voltag e during passiv e conditioning , however , di d no t var

ywit hPbB a t five-yea r follow-up . Becaus e th e childre n wer e ol d enough(6-1 2 years ) t o butto n pres s reliabl y a t five-yea r follow-up , an activ e formo f th e sensor yconditioning tes t wa s adde d t o th e electrophysiologica l battery . Childre n wer e aske d t o pres s a butto n a s quickl ya s possibl e whe n th e cartoo n wa s interrupted . Th e butto n pres s immediatel yrestore d th e cartoo n enabling childre n t o contro l th e duratio n o f th e interruption .P. 7

Figur e 2 illustrate s waveform s fromth e activ e an d passiv e tests . Slowwav e voltag e (negativity ) during th e CS-UC S interva l wa s muc hgreate r during activ e than passive conditioning . Th e activ e tes t thu s elicit s a mor e robus t electrophysiologica l respons e than th e passiv e test . Slow wav e negativit yduring activ e conditioning , moreover , increased linearl y wit hPbB level s o ^ childre n obtaine d a t five-yea r follow-un (Ott o e t al , 1985) . Therefore , th e activ e tes t als o appear s t o b e mor e sensitive than th e passiv e tes t t o th e effect s o f lea d exposur e i n children . I n th e replicatio n stud yw e wer e constraine d t o use d th e passive formo f th e sensor

yconditioning tes t becaus e man yo f th e childre n wer e considere d t o b e to o youn g (thre e an d fou r year s old ) t o butto n pres s reliably . No significan t relationshi p o f slowwav e voltag e 'an d PbB level s wer e foun

d i n thi s study . W e thu s faile d t o replicat e previou s finding s (Otto , e t a l 198l , 1982 ) i n a differen t grou p o f children . Inconsisten t finding s among th e fou r studie s ma yresul t fromsevera l factors . (l ) Result s o f th e five-yea r follow-u p stud y(Ott o e t al , 1985 ) indicat e tha t th e passiv e tes t i s no t particularl ysensitiv e t o lea d exposur e i n olde r children . Inconsisten t finding s maythu s b e du e t o th e relativ e insensitivit yo f th e passiv e test . (2 ) Differen t type s o f exposure s i n th e tw o group s o f subject s (e.g . secondar yoccupational _ exposur e v s Pb-base d paint ) ma yproduc e differen t neurobehaviora l con sequences . (3 ) Methodologica l difference s i n dat a analysi s betwee n earl y (Ott o e t al , 1981 , 1982 ) an d late r studie s mayhav e influence d findings . Stricte r criteri a fo r accepting singl e trial s i n slowwav e average s wer e use d i n earlie r studies . Mor e eye movemen t artifac t wa s tolerate d i n th e five

yea r follow-u

p an d replicatio n studie s t o increas e th e numbe r o f trial s i n average s fo r individua l children . Mor e trial s i n average s resul t i nP. 8

bette r reductio n o f nois e fromunrelate d electrica l activit yo f tb e brain . ^' ^ Previou s binding s na yhave bee n Typ e I statistica l errors — i.e. , slowwav e voltag e during passive conditioning ma yno t b e affecte d b ylow-to-moderat e P bexposure . Observatio n o f a linea r relationshi p o f P ban

d slowwav e negativit yduring activ e conditioning (Ott o e t al , 19 p 5) , however , argue s agains t thi s possibility . Pattern reversa l visua l evoke d potentials . T n vie wo f th e reporte d effect s o f neonata l Pbexposur e on visua l evoke d potential s i n rats , reviewe d above , pattern-reversa l visua l evoked potential s wer e adde d t o th e electrophysiologica l tes t batteryi n th e fiwi-yea r follow—u p an d replicatio n studies . Althoughflas hevoke d potential s wer e use d i n anima l studies , th e pattern-revers-a l tes t wa s velt'cte d fo r pediatri c assessmen t becaus e th e PRE Dha s prove n t o b e mor e sensitive than th e FE P i n mos t human testing application s (cf . Hallidayan d McDonald , 1981) . P l latencyha s bee n foun d t o b e th e mos t usefu l clinica l paramete r o f th e PREP . P l latencyi s delaye d i n case s o f opti c neuriti s (Hallida ye t al , 1972 ) an

d multipl e sclerosi s (Hallida ye t al , 1973) . W e predicted , therefore , tha t P l latencywoul d var ydirectl ywit hbloo d lead levels , bu t thi s measur e di d no t varywit hPbB level s i n eithe r th e five-yea r follow-u p o r replicatio n study . Severa l othe r PRE P measure s varie d wit hP bexposur e historie s o f children , however , a s show n i n figur e 3 . N1P 1 amplitud e increase d (fi g 3a ) ahd"N 2 latencydec'reasecTlfig . "3b ) i- n th e five-yea r follow-u

p stud y(Ott o e t al , 1985) . ' P1N 2 amplitud e (fi g 3c 1 ! ) (decrease

d wit h increasing Pbexposur e historyi n th e replicatio n study . Thes e finding s ar e problemati c fo r severa l reasons . (1 ) Result s o f th e tw o studie s ar e inconsisten t — i.e. , N1P 1 vs . P1N 2 amplitudes . (2 ) Result s o f th e five-yea r follow-u p stud ywer e contrar

yt o prediction . W eP. 9

hypothesize d tha t undu e P babsorptio n shoul d produc e effect s analogou s t o non-specifi c rtertyelinating diseas e ~ namely , increase d latencyan d decrease d amplitude . ' m h e observe d relationshi p 0*^lN l amplitud e an d p b B in th e replicatio n study , therefore , wa s consisten t wit hpredictions) . (3 ) From a statistica l poin t o f view , th e -findings ar e weak , ^h e multivariat e tes t fo r th e se t o f PRE P measure s in bot hstudie s wa s no t significant , although explorator

yunivariat e test s o f certai n parameter s wer e significan t a t th e .0 5 leve l o f confidence . Shorgi a e t a l (IQ83 ) an d Winnek e e t a l (IQ8I1 ) hav e als o use d PREP s i n evaluating th e effect s o f P bexposur e i n humans . Shorgi a e t a l reporte d increase d P l componen t latencie s i n Pbworker s compare d t o controls , bu t Winnek e e t a l foun d tha t P l latencyi n childre n decrease d wit hincreasing Pb

B withi n a rang e o f U t o 2 3 ug/dl . Th e mean PbB leve l o f P bworker s i n th e Sborgi a e t a l stud ywa s 62. 5 ug/dl . I t i s possibl e tha t P bha s a biphasi c effec t on nerv e conductio n velocit y (NCV) , facilitating NC V a t lowconcentrations , bu t slowing NC V a t moderat e t o highconcentrations . Result s o f lead studie s usin g PRE P measure s ar e summarize d i n Tabl e TV . Althoughw e faile d t o fin d effect s 0 ^ P bexposur e on P l latencya s predicte d an

d a s reporte d b

yWinnek e e t al , th e pattern-reversa l finding s o f th e Nordenhamstud yan d five-yea r follow-u p stud yar e consistent . PRE P latencie s decease d wit hincreasing PbB level s i n bot hstudies . Th e rang e o f PbB level s a t th e time o f PRE P testing i n th e Nordenham(1+-2 3 ug/dl ) an d five-yea r follow-u p (6-3 0 ug/dl ) studie s ma yb e a critica l factor . Th e rang e o f curren t PbB level s i n th e replicatio n (6-1* 7 ug/dl ) an d Shorgi a e t a l (pb-worke r mean PbB wa s 62. 5 ug/dl ) studie s wa s considerabl y greater . Furthe r researc hi s neede d t o clarif yth e inconsisten t finding s concerning th e effec t o f P bexposur e on visua l evoked potential s i n bot hP.1 0

human s an

d animals . Hearing an

d Brainstemauditor yevoked potentials . Littl e evidenc e concerning th e effec t o f Pbabsorptio n on hearing o r auditor yevoke d potential s in childre n i s presentl yavailable . Auditor yprocessing deficit s hav e bee n reporte d i n case s o f P bpoisoning (Jenkin s h Mellins , 195 7 ) an d asymptomati c exposur e (Perino & Ernhart , 1°7^ ; Needleman e t al , 1Q7Q) . Geuri t e t a l (I98l ) reporte d tha t BAEP s wer e no t affecte d b yP bexposur e i n childre n living nea r a P bsmelter , althoughth e lac k o f detai l i n tha t repor t preclude s drawing an yconclusions . W e therefor e conducte d a limite d audiometri c screening o f hearing threshol d (usin g a 2 KH z pur e tone ) an d recorde d binaura l BAEP s in th e five-yea r follow-u p an d replicatio n studies . Result s o f thes e studie s ar e summarize d i n Tabl e V . BAE P result s o f th e five-yea r follow-u p an d replicatio n studie s ar e show n i n figur e h. Result s o f th e forme r stud ywer e staight-forward : th e latencie s o f BAE P wave s II I an d V increased directl ywit hPbB historie s o f childre n (fig . kb) . Result s o f th e replicatio n stud ywer e mor e comple x an d onl ypartiall yconsisten t wit hearlie r findings . Tw o KH z hearing threshold s increase d significantl ywit hPbB (fig . ha.) a s di d I- V interpeak latency(a

n inde xo f centra l transmissio n tim e i n th e auditorypathway ) (fig . l*c) . Othe r parameter s o f th e BAEP , however , exhibite d a curvilinea r relationshi p t o P bexposur e history . Latencie s o f wave s III , V an d inter

peak latencyI-II I decrease d from6-2 5 ug/dl , bu t increase d a t PbB level s abov e 2 5 Ug/d l (figur e ^c) . Result s o f th e tw o studie s ar e consisten t fo r P bexposur e historie s abov e 2 5 ug/dl : BAE P latencie s increas e directl ywit hth e maxima l PbB value s foun

d i n th e children' s medica l records . Th e curvilinea r function s o f BAE P latencie s i n th e replicatio n stud ysuggest , however , a possibl e biphasi c effec t o f P bexposur e on nerve conductio n velocit yi nP.1 1

th e auditor

ypathwa

ywit hfacilitatio n a t Pb B level s belo w2 5 ug/d l an d slowing a t PbB level s above 2 5 ug/dl . Perhap s th e mos t intriguing finding fro m th e replication stud ywa s th e significan t increas e in hearing threshol d wit hincreasing Pbexposur e history . Thi s finding suggest s tha t P bexposur e impair s hearing an d th e periphera l segmen t o f th e auditor ypathway . Thi s preliminar yfinding i s o f considerabl e interes t i n vie wo f th e well-documente d associatio n o f childhoo d lead poisoning , menta l retardatio n an d subtl e learning disabilitie s (cf . USEPA , 1977) . Aselective hearing los s occurring i n earl ychildhood tha t remain s undetecte d coul d resul t i n speec hpatholog yan d learning impairmen t a s th e chil d grows . Suc hproblem s frequentl yar e no t identified unti l th e chil d reache s schoo l ag e an d demonstrate s performanc e deficiencies . Recen t confirmatio n o f th e effec t o f lead absorptio n on bearing threshold s ha s bee n foun

d i n th e NHANE S I I stud y(Schwart z an

d Otto , in preparation) . Andiometri c testing o f 500 0 youn g peopl e age d ht o 1 9 year s ol d wa s performe d wit hpur e tone s a t 500 , 1000 , 200 0 an d 1+00 0 Hz . Hearing threshold s increase d significantl ywit hPbB leve l a t th e thre e lowes t frequencie s tested . BAE P findings , moreover , sugges t tha t P bexposur e affect s centra l a s wel l a s periphera l segment s o f th e auditorypathway . Th e adjustmen t o f clic k intensit yt o obtai n equa l sensatio n level s i n childre n teste d i n bot hstudie s doe s no t permi t u s t o verif yth e apparen t hearing threshol d effec t using wav e I latencybecaus e wav e I latencyvarie s wit h clic k intensit y. I n orde r t o evaluat e th e validit yan d generalit yo f ou r findings , a comprehensiv e audiometric , BAE P an d speechassessmen t o f a n independen t sampl e o f childre n a t ris k fo r lea d poisoning shoul d b e under

taken .P.1 2

1 0

FUTUR E DIRECTION S I NNEUROBEHAVIORA L LEA D RESEARC H

1 . *T ee d fo r longitudina l studies . Evaluation o f th e neurobehaviora l effect s o f lea d exposur e i n humans , particularl ypsychometri c dat a i n children , ha s bee n hampere d b yth e cross-sectiona l natur e o f mos t previou s studies . Lead exposur e historycanno t b e determine d froma singl e bloo d lea d measure , th e mos t widel yuse d metri c o f lea d exposur e i n cross-sectiona l studies . Toot hlea

d measure s provid e an integrate d measur e o f exposur e histor yi n children , bu t th e limite d availabilit yo f deciduou s teet han d th e analyti c complexit yo f thi s measur e limi t it s application . Longitudina l studie s i n whic hchildre n o r worker s ar e sample d a t regula r interval s t o documen t exposur e historyove r an extende d perio d o f year s offe r th e bes t solution . Th e Cincinnat i Prospective Lead Projec t describe d elsewher e i n thi s volume i s an excellen t exampl e o f th e kin d o f longitudina l stud yneeded t o clarif y th e significanc e an d persistenc e o f behaviora l an d electrophysiologica l effect s o f P bexposur e reporte d i n previou s cross-sectiona l studies . 2 . Nee d fo r comprehensive auditoryassessment . Result s o f our recen t studie s (Otto , e t al , 1985 ; Robinson , e t al , 1985 ) sugges t tha t lea d ex posur e affect s periphera l an d centra l segment s o f th e auditor ypathway . Hearing threshold s an d centra l conductio n time wer e bot haltere d i n th e replicatio n stud

y(Robinson , e t al , 1985) . Th e implication s o f subtl e lead-relate d hearing los s i n youn g childre n fo r subsequen t speec han d learning disorder s wer e note d above . Audiometri c evaluation s ar e simple , standardize d an

d fairl yinexpensive t o administer . BAE P testing i s als o fairl ysimpl e an

d standardized , thoughsomewha t mor e expensive tha n audiometry . W e recommen d th e additio n o f suchtest s t o futur e pediatri c lead studie s an

d t o lead worke r monitoring programs .P.1 3



### 1 1

Result s o f BAE* 3 testing indicat e tha t thi s electrophysiologica l measur e i s ver

ysensitive t o th e effect s o " lea d exposure . BAE P testing provide s valuabl e information abou t centra l conductio n i n the auditor y pathway , informatio n tha t canno t b e obtaine d fromaudiometri c testing . Furthe r BAE P studie s i n lead-expose d childre n an d worker s ar e needed , however , t o clarif your previou s findings . Doe s lead exposur e reall y produc e a biphasi c dose-dependen t effec t on auditor yfunctio n i n children ? I s th e effec t o f lead on auditoryfunctio n reversible ? Ar e childre n mor e susceptibl e t o lead-relate d hearing impairment s than adults ? Comprehensive audiometric , electrophysiologica l an d speec hassessment s i n childre n an d adult s ar e neede d t o resolve thes e questions . 3 . Need fo r scotopi c visio n testing . Studie s o f visua l evoked potential s i n human s an

d animal s al l sugges t lead-relate d alterations , althoughnumerou s inconsistencie s wer e note d above . Furthe r studie s o f visua l functio n i n human s an

d animal s ar e neede d t o resolve thes e inconsistencies . Pattern reversa l visua l evoke d potentials , however , ma yno t b e a particularl y sensitiv e measur e t o use . Aserie s o f i n vitr o (^o x h Sillman , 1979 ; Sillman e t al , 1982 ; Tessier-Lavign e e t al , 1985 ) an d i n viv o (Bushnel l e t al , 1977 ; Fo xe t al , 19 R 5 ) anima l studie s sugges t tha t rod s ar e mor e susceptibl e than cone s t o P btoxicity . Tha t is , P baffect s nigh t (scotopic ) visio n mor e than da y(photopic ) visio n i n anima l models . I f lead alter s rod , mor e than con e functio n i n humans , the n PREP s ar e unlikel yt o showan yconsisten t effec t sinc e th e PRE P reflect s priraarillycone-mediate d visio n (Sokol , 1976) . Test s o f periphera l an d dark-adapte d visio n i n lead-expose d human s ar e neede d t o resolve thi s question .P. M

h. Need fo r assessmen t o f cognitive function . A n are a o f considerabl e controvers yha s hee n th e *»ffect o f l»r Mahsorntio n o

n cognitive 'levelonren^ an d intelligenc e in childre n (c' . contribution s o f Bornschein , Dietrich , Ernhart , Grant , McBride , Smith , Vimpani , Winnek e an d Yul e in thi s volume) . Interpretatio n o f cross-sectiona l pediatri c result s ha s bee n cloude d b yth e confounding effect s o f sociocultura l variables . Recen t wor k fro mour laborator

y(Haw k e t al , 1985 ) demonstrate d an l8-poin t spea d in full

scal e Stanford-Bine t I Q score s acros s th e p bexposur e rang e (6-1* 7 ug/dl ) i n thre e t o seve n yea r ol d childre n whe n socioeconomi c statu s wa s controlle d i n th e experimenta l design . W e limite d subject s t o a subse t o f th e U.S . populatio n considere d t o b e a t highes t ris k fo r lead poisoning—i.e. , low-income Blac k childre n fro n SE S classe s IV an d V on th e Hollingshead Scale . Aparalle l statel yo f ou r grou p ha s bee n t o us e electrophysiologica l indice s o f sensor

yconditioning tha t ar e considere d t o b e independen t o f standard I Q measure s an d t o b e fre e o f th e sociocultura l biase s o f I Q tests . Earl yresult s (Ott o e t al , 19^1 ; 1982 ) suggeste d tha t slowwav e voltag e measure s obtaine d during sensor yconditioning wer e sensitive t o lead exposur e i n childre n an d wer e uncorrelate d wit hSES , materna l IQ , chil d I Q o r Caldwel l H.O.M.E . rating s o f care-giving practices . A s note d previously , slo wwav e voltag e during passiv e conditioning di d no t var ywit hP bexposur e historyi n olde r childre n (Ott o e t al , 1985 ) o r in an independen t sampl e o f thre e t o seve n yea r ol d children . Thes e inconsisten t finding s sugges t th e nee d fo r mor e sensitive an d reliabl e electrophysiologica l measure s o f cognitive functio n in children . Preliminar

yresult s wit ha modifie d tes t indicat e tha t th e additio n o f a moto r respons e improve s th e effectivenes s o f th e sensor yconditioning tes t markedl v(Ott o e t al , 1985) . Developmen t o f mor e sophisticate d event 

### 1 2

### 1 3 P.1 5

relate d slowpotentia l test s incorporating a P30 0 paradig mtha t i s widel yuse d in cognitive psychophysiolog y(r. r . Uonchi n e t a 1 , 10^8 ) Recurrentl yi n progress . Oourchesn e e t a l ^1983 , 1085 ) have demonstrated th e utilit yo f suchtest s in norma l an d developmentall ydisordered children . Th e clinica l utilit yo f event-relate d endogenou s potential s ha s bee n mos t clearl ydemonstrate d i n studie s o f Alzheimer' s diseas e an d aging (Squire s e t al , 1980) . "'h e latencyo f the P30 0 wave , a positiv e ER P tha t peak s betwee n 30 0 an d 90 0 mse c afte r presentatio n o f an in

frequen t o r meaningfu l stimulus , i s delaye d i n patient s wit hAlzheimer' s diseas e relative t o controls . P30 0 latencyha s bee n associate d wit h stimulu s evaluatio n time o r "menta l chronometry " (Kuta s e t al , 1977) . P30 0 testing can b e brie f (1 0 t o 2 0 minutes ) an d can b e administere d simpl y i n standardize d formwit hcommerciall yavailabl e equipment , ""h e applicatio n o f P30 0 method s i n neurotoxicit ytesting ha s bee n reviewe d recentl yb y Harbi n (1985) . Althoughth e effec t o f lead exposur e on cognitive developmen t ha s bee n studie d extensivel yi n children , studie s o f lead-expose d adult s usuall y focu s on periphera l nervou s systemfunction . Symptom s o f acut e lead poisoning i n adults , however , includ e dullness , irritability , poo r • attentio n span , headaches , an d los s o f memor

y(reviewed i n USEPA , 19.85) . Th e syndrom

e o f lead encephalopath yi n adult s i s well-known , bu t fe weffort s hav e bee n mad e t o stud yth e effect s o f asymptomati c lead exposur e on cognitiv e functio n i n adults . I n vie wo f increasing evidenc e tha t lea d affect s cognitive developmen t i n childre n a t lowe r level s o f exposur e than previousl ythough t (USEPA , 1985) , furthe r systemati c stud yo f cognitive functio n i n lead-expose d adult s i s clearl yneeded . Classica l neurobehaviora l testing method s (e.g. , Valciuka s e t al , 1978) , computerize d behaviora ltes t batterie s (e.g. , Bake r e t al , 1985 ) o r endogenou s ER R method s noted above woul d be appropriat e fo r suchstudies . SUMMAR Y Seiisor yevoked an

d slowbrai n potential s have bee n use d t o stud yth e effect s o f lea

d absorptio n o n CNS functio n i n bot hhumaii s an d animals . Result s o f thes e studie s wer e reviewe d an d suggestion s fo r futur e neuro behaviora l lea

d studie s wer e made . Althoughthe result s o f individua l studie s sugges t tha t thes e measure s ar e ver ysensitive t o the effect s o f lea d absorption , man

yinconsistencie s among studie s wer e noted , particularl v wit hregard t o visua l evoke d potentials . The pattern-reversa l VEP , whic h reflect s primaril yfovea l vision , ma yb e an inappropriat e measur e o f lea d effect s i f rod s ar e mor e vulnerabl e than cone s t o exposure . Failur e t o replicat e earlie r report s o f the relationshi p o f slo wwav e voltag e an d lea d exposur e suggest s tha t the passive sensor yconditioning tes t i s no t a particularl ysensitive measur e o f lea d effect s i n children . Increased auditor ybrainstemE P latencie s wit hblood lead level s above 2 5 \ivfil wer e reporte d i n two pediatri c studies . Furthe r studie s o f sensor y evoke d an

d slowpotential s i n lead-expose d animal s an d human s ar e needed t o clarif yan

d exten d the promising , bu t limited evidenc e presentl yavailable . P.1 6



### 1 4ACKNOWLEDGEMENT S 

### 1 5

Suppor t fo r the Mort hCarolina pediatri c lea d studie s wa s provided b yNIEH S Gran t ES-OHOl* , E^ AContrac t 68_Q2_1702 , an d E DACollaborative Agreemen t CR8099° 2 wit hth e Universit yo f Nort hCarolina . Alarg e an d dedicate d staf f wa s require d t o collec t an d analyz e thi s data . Co

principa l investigato r wa s Stephe n Schroeder , Ph.D. , Universit yo f Nort h Carolina Schoo l o f Medicine . Majo r contributor s include d V . Benignus , S . Bauman

n an d 0 . Robinso n (electrophysiology) ; C . Mila r an d B . Haw

k (psychometrics) ; P . Musha k (analyti c chemistry) ; K . Muller , D . Kleinban m an d C . Barto n (statistics) . Th e assistanc e o f Lenoir , Ne wHanove r an d Wak e Count yHealt hDepartment s i n recruiting subjects , J . Nichol s fo r manuscrip t preparation , an d C . Rodrigue z fo r graphic s i s gratefull y acknowledged .P.1 8

1 ^

REFERENCE S 1 . Rak*>r , E.L. , T ,et.z , P. , »^> r , A. , Shp.lat , S. , P^n^n'ra . D . nnd Lyndon , M . 'l f ' q 5^ . "ompater-base d neurobehaviora l evaluation syste n fo r occupationa l an d environmenta l epidemiology : Methodolog yan d validatio n studies . Neurobehav . Toxicol . m eratol. , 7 : 369-377 . 2 . Bushnell , ° . , Bowman , R. , Allen , J . fc Marlar , R . (1977) . Scotopi c visio n deficit s in young monkey s expose d t o lead . Science , 196 , 333-335 . 3 . Courchesne , E . (19^3) . Cognitive corrnonent s o f th e event-relate d brai n potential : Change s associate d wit hdevelopment . Tn : A.W.K . Gaillard fc W . Bitte r (eds . ^ Tutorial s i n FR P Research : Endogenou s Components . North-Hollan d Publishing Co. , Amsterdam , pp . 329-3l*H . 1* . Courchesne , E. , Lincoln , A. , Killman , B . fc Galambos , R. , (1985) . Event-relate d brai n potentia l correlate s o f th e processing o f nove l visua l an

d auditor

yinformatio n i n autism . _£ . Autis mDev . Disorders , 15 : 55-75 . 5 . Donchin , E. , Ritter , W. , f t McCallum , W . C . (1978) . Cognitive psycho

physiology : Th e endogenou s component s o f th e ER p . In' : E . Callaway , P . "Yietin

g fc S . Koslow(eds. ) Event-relate d Brai n Potential s i n Man . Academi c Press , Ne wYork , pp . 31*9-1*12 . 6 . Feeney , D. , Longo , J. , Cosden , M. , Zenick , H . fc Padich , R . (1979) . Detectio n o f th e effect s o f lea d exposur e b

yvisua l evoked respons e latency . Physiol . Psychol. , 7 : lU3—1U5

- 7 . Fox , D. , Lewkowski , J . & Cooper , G . (1977) . Acut e an d chroni c effect s o f neonata l lead exposur e on th e developmen t o f th e visua l evoked respons e i n rats . Toxicol . Appl . Pharmacol. , ^0 : Hl*9-k6l . 8 . "^ox , D. , Lewkowski , J . fc Cooper , G . (1979) . Persisten t visua l corte x excitabilit yalteration s produce d b yneonata l lead exposure . Neurobeh_ . Toxicol. , 1 : 101-106 . 9 . Fox , D . fc Sillman , A . (1979) . Heav ymetal s affec t rod , bu t no t cone , photoreceptors . Science , 206 : 78-80 . 10 . ^ox , D. , Farber , D. , Chu , L. , fc Stein , J . (1985) . Rod photoreceptor s ar e selectivel yaltered.by.lead : Electrophysiological , biochemica l an d morphologica l studies . Th e Toxicologist , 5 : 8 1 (abstr) . 11 . Geurit , J. , Meulders , M. , Amand , 0. , Roels , H. , Buchet , J. , Lauwerys , R . Bruax , P. , Claeys-Thoreau , F. , Ducoffre , G . fc Lafontaine , A . (1981) . Lead neurotoxicit yi n clinicall yasymptomati c childre n livin g i n th e vicinit yo f an or e smelter . Clin . J^oxicol^. , 18 : 1257-1267 . 12 . Halliday , A. , McDonald , W . fc Mushin , J . (1972) . Delaye d visua l evoke d respons e i n opti c neuritis . Lancet , 1 : 982-985 .P.1 9

1 7



### 13 . Halliday , A. , McDonald , W. , fc Mushin , J. , (1973) . Visua l evoke d respons e i ndiagnosi s o- f multipl e sclerosis . Br . Med . £ . h: 661-661; . l's . Halliday , A . fc "cDonajd , W . (1981) . Visua l evoke d potentials . In : "Clinica l Neurophysiology " (E . Stalher p fc R . Young , eds^ , p p 228-258 , Buttersworth . 15 . Harbin , T . (1985) . Th e lat e positiv e componen t o f th e evoke d cortica l potential : Applicatio nt o neurotoxicit ytesting . Neurobehav . m 

### oxicol . Teratol . (i npress) . 16 . Hawk , B. , Schroeder , S. , Robinson , 0. , Otto , D. , Mushak , P . fc Barton , C . (1985) . Relatio no f lea d t o cognitiv e functio no f childre n a t ris k fo r sociocultura l menta l retardation . Am . £ . Ment . Defic . (i npress) . 17 . Jertkin , D. , fc Mellins , R . (I95u) . Lea d poisonin g i nchildren . Arch . Neurol . Psychiat. , 77 : 70-80 . 18 . Kutas , M. , McCarthy , 0. , Donchin , E . (1977) . Augmentin g menta l chronometry : Th e P30 0 latenc yo nstimulu s evaluatio n processes . Psychophysiology , 21 : 171-186 . 19 . Needleman , H.E. , Gunnoe , 0. , Leviton , A.. , Reed , R. , Peresie , H . , Maher , C , fc Barrett , P . (1979) . Deficit s i npsychologi c and classroo nperformanc e o f childre nwit helevate d dentin e lea d levels . Ne wEngl . £ . Med . , 300 : 689-605 . 20 . Otto , D. , Benignus , V. , Muller , K . fc Barton , C . (loRl) . Effect s o f ag e and bodylea d burde no nCN S functio ni nyoun g children . I . Slo w cortica l potentials . Electroenceph . Clin . Neurophysiol. , 52 : 229-239 . 21 . Otto , D. , Benignus , V. , Muller , K. , Barton , C , Seiple , K. , Prah , J . fc Schroeder , S . (1982) . Effect s o f lo wt o moderat e lea d exposur e o nslo w cortica l potential s i nyoun g children : ^wo-yea r follow-u p study . Neurobehav . Toxicol . Teratol. , h: 733-737 . 22 . Otto , D. , Robinson , G. , Baumann , S. , Schroeder , S. , Mushak , P. , Kleinbaum , D. , fc Boone , L . (1985) . Five-yea r follow-u p studyo f childre nwit hlow

to-moderat e lea d absorption : Electrophysiologica l evaluation . Environ . Res. , 38 : (i npress) . 23 . Perino , J. , fc Ernhart , CB . (l97n) . Th e relatio n o f subclinica l lea d leve l t o cognitiv e an d sensorimoto r impairmen t i nBlac k preschoolers . £ . Learn . Dis. , 7 : 6l6-620 . 2l* . Robinson , G. , Baumann , S. , Kleinbaum , D. , Barton , C , Schroeder , S. , Mushak , P. , Otto , D . (1985) . Effect s o f low-to-moderat e lea d exposur e o nbrainste mauditor yevoke d potential s i nchildren . Environmenta l Health , Doc . 3 (Neurobehaviora l Methods i nOccupationa l an d Environmenta l Health) , Worl d Healt hOrganization , Copenhagen , p p 177

- 1R2 7 :P.2 0



### 1 8

25 . Sborgia , G. , Assennato , 0. , L'Abbate , N. , DeMarinis , L. , Paci , C , DeNicolo , M. , Demarinis , G. , Montrone , N. , Ferrannini , E. , Specchio , L . , M asi , G . fc OiWov-s ^ n . 'io.°-5> . ! -owr' ,v i 0 ^siv p <T>oronVvp- : o1r.T-.rn" > evaluation o' - .lead-exnose d workers . In : Neurobehaviora l Method s i n Occupationa l health , 'R . Gilioli , M . , Cassit o fc V . Foa , eds. \ pp 283-29U , p ercano n D ress , London . 26 . Schroeder , S . , Hawk , B. , Otto , D. , Mushak , P . fc Hicks , R . (1985) . Separating th e effect s o f lea d an d socia l factor s o

n TO . Environ . Res . , 38 , (in press) . 27 . Schwartz , J . fc Otto , D . (1985I . Blood lea d levels , hearing threshold s an d neurologica l developmen t in NHANE S I I children , (in preparation) . 28 . Sillman , A. , Bolnick , D. , Bosetti , J. , Haynes , L . fc Walter , A . (1982) . Th e effect s o f lea

d an d o f cadmiu

mo n th e mas s photorecepto r potential : th e dose-respons e relationship . Neurotoxicology , 3 : l 7 9-19l+ . 29 . Sokol , S . (1976) . Visuall yevoke d potentials : Theory , technique s an d clinica l applications . Surv . Opthalmol. , 21 : lR—UU . 30 . Squires , K.C. , Chippendale , J.S. , Wrege , D.S. , Goodin , fc Starr , A . (1980) . Electrophysiologica l assessmen t o f menta l functio n in aging an d dementia . In : Aging i n th e 1980's : Psychologica l Issues , edite d b

yL.W . Poon . Washington , DC : American Psychologica l Association , pp . 125-13U . 31 . Tessier-Lavigne , M. , Mobb , P . fc Attwel l (1985) . Lead an d mercur

y toxicit yan

d th e rod ligh t response . Invest . Ophthal . Vis . Science , 26 : 1117-1123 . 32 . U.S . Environmenta l Protectio n Agenc y(1985) . Ai r Qualit yCriteri a fo r Lead , Vol . IV , FPA-600/8-83-028 A(in press) . 33 . Valciukas , J. , Lilis , R. , Eisinger , J. , Blumberg , W. , Fishbein , A . fc Selikoff , I . (1978) . Behaviora l indicator s o f lead neurotoxicity : Result s o f a clinica l fiel d study . Int . Arch . Occup . Environ . Health , 1+1 : 217-236 . 3U . Winneke , G . (1979) . Modificatio n o f visua l evoke d potential s i n rat s afte r long termbloo d lead elevation . Activ . Nerv , Sup . ^ p raha) , 21 : 282-281+ . 35 . Winneke , G. , Beginn , TI. , Ewert , T. , Havestadt , C , Kramer , U. , Krouse , Ch. , Thron , H . fc Wagner , H . (198I+) . Studi e zur Erfassung subklinische r Bleiwirkunge n au f da s Nervensystemvo n Kinder n mi t vekannte r pranatale r Expositio n i n Nordenham . Schr.-Rein e Verei n Wabolu , 59 : 215-229 .TABL E I . EFFECT S O F NEONATAL LEA D EXPOSUR E ONFLAS H EVOKE D POTENTIAL S (w.p) T NRA^ P

;TUD Y SPECIES/NUMBE R O F ANIMAL S EXPOSUR E INFORMATION SIGNIFICAN T RESULT S "o xe t al , 197 7 Long-Evan s ( 6 animals/treatment / age ) Newbor n rat s expose d t o P b vi a dam' s milk ; drinking wate r o f dam s containe d 0.2* ' P bacetate . Exposur e cease d a t weaning (2 1 days) . Mea n blood/brai n P blevels : Control s Expose d d y2 1 6/ 7 65/5 3 Pg/d l d y9 0 5/1 1 7/1 3 1 . FE P latencie s (P l , w l ,P ? ,*>2 ) wer e longe r in Pb-expose d rat ^ during developmen t (day s 9-1? , 16 , 20 ) an d a s adult s (da

y°0) . 2 . Developmen t o f EE P component s wa s delaye d in Pb-expose d nts . 3 . Latenc yrecover yt o pa i re

d flashe s wa s decrease d i n Pb-exr'^ne d rat s a t 9 0 days . 1* . Frenuency-following respons e t o repetitiv e "lashe s wa s •iecreaser ' i n Pb-expose d adul t rats .

o xe t al , 197 9 Long-Evan s 6 control s 6 expose d

?ene ye t al , 197 9 C D rat s

9 control s 8 expose d Same day-O 0 rat s a s abov e

Newbor n rat s expose d t o P b vi a dam' s milk , potentia l dam s receive d 75 0 mg/k g P b acetat e dissolve d in drink

ing wate r fromda

y2 1 unti l weanin g o f pups . N o bloo d o r P bdat a provide d fo r animal s tested . Ph R level s fromduplicat e sampl e ex pose d dams wer e 11 7 ug/d l a t weaning vs . '

> ug/d l fo r contro l dams . Estimate d PbB level s o f al l animal s a t test ing-was—<l t ug/dl . Rat s expose d neonatall yt o P bshowe d increase d cortica l excitabilit y(P2 / R l amplitud e rati o o f resoonse s t o paire d flashes ) compare d t o control s

FE P latency(P 2 only ^ i n ~*n_R o day

ol d rat s wa s shorte r i n P ^-expose d than contro l animals .•UD Y SPECIES/WTIMRER

O F ANIMAL S EXPOSUR E INFORMATIO N RESULT . innek e (1979 ) Wista r 1 0 animals / treatmen t Fo r 6 0 day s prio r t o mating : dams fed 1

* diets : control , 750 , 2260 , o r 67)i 0 ppmPb-acetate . Observe d p b R level s in dams were : <5 , 2U , 5 3 an d 8 7 ug/dl . Pb R level s in offspring afte r 110-19 0 d o f postnata l Pb

feeding : <5 , 29 , '*0 , an d 6 b Ug/dl . Pat s wer e teste d at 150-19 0 day r o f age . ^E P amplitude s 'N1,N1P^ ) wer e lowe r i n tw o high'--. t exposur e group s than controls , "hreshol d effec t leve l o f 30-H 0 i^' d noted . No Pb-relate d ^-lhenc y effect s found .

r oP.2 3

TABL E II . SUMMAR

Y O F EVALUATION S

I . Exposur e Evaluatio n A . Fantu s Lead D oisonin g Ouestionnair e B . Rlood Lead 'Ph*>^ : ^laneles s Atomi c Absorptio n Spectrometry C . Fre e Erythrocyt e Protoporphyri n (FEP ) II . Medica l Evaluatio n A . M edica l Histor y B . Pediatri c Neurologica l Examinatio n C . Growth : Height , Weight , Head Circumferenc e D . La bTests : BDS , WBC , RBC , Hgb , HCT , MCV , MCH , MCH C III . Electrophysiologica l Evaluatio n A . Slo wCortica l Potential s during SensoryConditioning B . BrainstemAuditoryEvoke d Potential s C . Pattern-Reversa l v isua l Evoke d Potential s IV . Psychometric-Behaviora l Evaluatio n A . Stanford-Bine t Intelligenc e ^est-Revise d (Children ove r 3 0 months ) B . Bayle yScale s o f Menta l Developmen t (Children unde r 3 0 months ) V . Demographi c Covariat e Evaluatio n A . Materna l IQ : Amraon s Quic k Tes t p r Peabod yPictur e VocabularyT e s t Revise d B . Socioeconomi c Status : Hollingshead ''Vo-Factor Inde x C . Qualit yo f Caregiving Environment : Caldwe.ll' s Home Observatio n fo r Measuremen t o f th e Environmen t D . Chronologica l Ag e E . Se xTARL E III . RELATIONSHI P O F SLOWWAVE VOLTAG E AND Pb R LEVEL S DURIN

GSENSORY CONDITIONIN G

STUDY NUMBE R O E

SUBJECT S I N DAT AANALYSI S AGE (YEARS ) Pb

R AT TESTIN G (ug/dl ) TYP E O F

CONDITIONIN

G PPTULT' - NITIA L EVALUATIO

N Ott o e t al , 1981 )

-YEA R FOLLOW-U P Ott o e t al , 1982 ) »»1

2 8 1- 6 6-5 5

3- 1 ll»-3 9 PASSIV ESLO " WAV ? "Of/PAGE'.''"TE D ! (3 5 trials ) A S ALINEAREUNCT.ir

—OFI Pb B AN D AG EI PASSIVE (10 0 trials ) 

## I

SLOWWAVE VOLTAG E v-.^IE D ! AS ALINEA

R PirMPTTO " O F ! Pb R AN D AGE DURIN

G' ^T R TRTAI. S (hl-lOO ) ONT, -

- '

-YEA R FOLLOW-U P Itt o e t al , 1985 ) I1 8 6-1 2 6-3 0 PASSIVE (10 0 trials ) AND ACTIVE (5 0 trials ) AS AL I "EA R FUMC'riP' 1 ' O F CURREN T Ph B DURIN G ACTIVE , Rtr

n NO T DU

R •"•''I PASSIVE CONDITIONIN G ^PLICATIO

NSTUDY )tt o e t al , in -(reparation ) 6 8 3- 7 6_>i 7 PASSIV E (10 0 trials ) SLO WWAV EVOr, ,T, AO ED nNO

T VAR YWT ,n > TPb RLEVEL " O

R AG E

t o J *TABL E IV . RELATIONSHI P O F PATTERN-REVERSA L VISUAL EVOKE D PO^EN^IAL MEASURE S AN D Pb R

STUD Y NUMBE RO F STTBJECTS I N DAT AANALYSI S AG E

(YEARS ) PbB AT

TESTIN G (ug/dl ) RESULT S i e t a l (1983 ) 3 1 Expose d 3 7 Contro l 14 2 62. 5

19. 0 REPORTE D INCREASE D P l LATENCIE S INPb-WOR 1 ' ,-c ? S COMPARE D T O CONTROL S

e t a l(1985 ) 12 2 6- 7 H-2 3 REPORTE D DECREASING^ 1 LATENC YWI^ u I'IPRE ; TN G Pb R Follow-ti p ?t . al , 1985 ) 

### 1* 3 6-1 2 6-3 0 N1P 1 AMPLITUD E INCREASE D AN D N p LATENC Y DECREASE D WIT H INCREASIN GORIGINA

L Pb R itio n Stud y 

### 7 0 

### 3- 7 6-H 7 P1N 2 AMPLITUD E DECREASE D "TT H INCREASIN G^'. R (MAXIMA L = 6-5 6 ug/dl )

:y>TABL E v . RELATIONSHI P O F BRAINSTE MAUDITORY EVOKE D POTENTIA L MEASURE S AN

D Pb R T NCHILDRE "

STUDY NUMBE R O F

S'TRJECT S I N DAT AANALYSI S AGE

(YEARS ) P b(ug/dl ) a . CURREN

T b . MAXIMA

L RESULT S

-YEA R OLLOW-UP ">tt o e t al , 1985 ) 1* 5 6-1 2 a . b . 6-^ 0 6-5 0

'^PLICATIO

NSTUDY ">tt o e t al , i n oreparation ) 6 5 3- 7 a . 6-^ 7 b . 6-S 6 1

t WAVE II I AN

D V LATENCIE S TNCP 1 ' - '"E D ! LINEARLY WITH INCREASIN GM-'VXP".', , I BUT NO T CURREN

T Pb R I (1 ) HEARIN

G THPESHOL D INOREAS' - ' ' LTNEARLY WITH Pb

R (OMRREN" ' AN

D MAXIMAL) . (2 ) WAVE I LATENCY DECREASE D LINEARLY WI^ H Pb

R (CURREN' " AN

D MAXIMAL) . (3 ) WAVE TTT , V

LATENCIE S AN

D TPL I-IIT , T- , r SHOWE D OURVU.r'^A R RELATIONSHI P T O Ph

P (MAXT"A L ONT.Y) . (ll ) TP L I_

V INCREASE D LT*'EARL- 7 WITH Pb R (MAXIMA

L ONLY ) 

# r r.4P.2 7

? 5

FIGUR E LEGEND S "J,r.i-->i1 . "r.'.e:•:;-. • M••• : c"'e;: ! , s o' ~ a^ s an* ) bloo d lfif.i l ievr-;Is o n :;.'.o

v wav e voltag e i n childre n durin g passiv e sensor yconditioning . Predicte d slo wwav e voltae e and OS 1 * , confidenc e limit s ar e depicte d a s a functio n o f origina l bloo d lea d level s a t th e extrem e age s o f subject s a t initia l evaluation . (.Adapte d fro mElectroenceph . Clin . Neurophysiol. , IQ81 , S2 : 235^ . Figur e 2 . Summar yaverage s o r slo wpotential s observe d a t r ronta l

(•^z) , centra l (Cz ^ an d parieta l recordin g site s i n childre n durin g activ e an d passiv e sensor yconditionin g (five-yea r follow-u p evaluation^ . Th e electro-oculogra m(FOG ) recorde d fro melectrode s abov e an d belo wth e righ t ey e i s als o shown . Horizonta l bar s abov e average s depic t interval s durin g whic h conditione d (CS ) an d unconditione d (UCS ) stimul i wer e presented . Slo wwav e measuremen t interval s (SW I and SW2 ) ar e designate d byvertica l lines . Not e tha t slo wwav e voltag e i s muc h greate r durin g activ e tha n passiv e conditioning . Figur e 3 . Scatte r plot s an d regressio n line s fo r N1P 1 amplitud e (a) ,

N 2 latenc y(b ) an d P1N 2 amplitud e (c ) o f th e patter n reversa l visua l evoke d potentia l a s a functio n o f maxima l bloo d lea d level s o f children . (a ) and (b ) wer e obtaine d fro mchidre n age d 6 t o 1 2 year s i n th e five-yea r follow-u p study . (c ) wa s obtaine d fro mchildre n age d 3 t o 7 year s i n th e replicatio n study . Figur e 1* . Scatte r plots , regressio n lines , an d 95* > confidenc e limit s o f

(a ) hearin g threshold , (b ) BAE P wav e V latencie s o f boy s an d girl s i n th e five-yea r follow-u p study , an d (c ) BAE P wav e V an d interpea k V- I latencie s o f childre n i n th e replicatio n study a s function s o f maxima l bloo d lea d levels . Hearin g threshold s wer e determine d audiometricall yusin g a 2 KH z pur e ton e i n th e replicatio n study . Alinea r relationshi p o f wav e vlatency^an d Pb B wa s foun d i n childre n age d 6 t o 1 2 year s (b) , whil e a curvilinea r relationshi p wa s foun d i n childre n age d 3 t o 7 year s (c^ .• yr-mfrrfTwirj

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